Increasing chromosome 1 copy number parallels histological progression in breast carcinogenesis

Chromosome 1 copy number in the benign breast lesions hyperplasia and atypi cal duct hyperplasia (ADH) was investigated using fluorescence in situ hybr idization on paraffin sections. Progression of chromosome 1 changes occurri ng in parallel with histological progression from normal through hyperplasi a and ADH to ductal carcinoma in situ (DCIS) and invasive carcinoma was als o assessed, both overall and within individual patients. The mean signal nu mber for normal cells was 1.14, while that for hyperplasia was 1.56 and ADH was 1.5, while values for DCIS of 1.95 and invasive duct carcinoma of 1.79 , were higher (P < 0.001). Six of the seven cases also showed a significant trend towards an increasing proportion of cells with greater than 2 signal s per nucleus occurring with histological progression (P< 0.001). These res ults support the concept that benign proliferative breast disease is a biol ogical precursor of in-situ and invasive ductal carcinoma, the early histol ogical changes possibly indicating a field effect with further genetic chan ges required for the development of a malignant phenotype. (C) 2000 Cancer Research Campaign.